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Phorbol ester-induced U-937 differentiation: effects on integrin alpha(5) gene transcription
B K Boles1, J Ritzenthaler, T Birkenmeier
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Veterans Affairs Medical Center and Emory University School of Medicine, Atlanta, GA 30033, USA.
Summary
Tumor promoter phorbol 12-myristate 13-acetate (PMA) increases alpha(5)beta(1) integrin expression in human monocytic cells. This enhances cell adherence to fibronectin, potentially regulating immune cell function in lung injury.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Lung injury increases fibronectin (FN) matrix deposition.
- Activated monocytic cells express FN integrins, like alpha(5)beta(1), crucial for cell-matrix interactions at injury sites.
Purpose of the Study:
- To investigate the effect of phorbol 12-myristate 13-acetate (PMA) on alpha(5)beta(1) integrin expression in U-937 human promonocytic cells.
- To elucidate the molecular mechanisms regulating alpha(5)beta(1) expression.
Main Methods:
- U-937 cells treated with PMA and lipopolysaccharide.
- Analysis of alpha(5)- and beta(1)-subunit mRNA and protein expression.
- Reporter gene assays to study alpha(5) gene transcription.
Main Results:
- PMA significantly increased U-937 cell adherence to fibronectin.
- PMA upregulated both alpha(5) and beta(1) integrin subunit mRNA and protein expression.
- PMA induced alpha(5) gene transcription via protein kinase C in a manner independent of AP-1.
Conclusions:
- PMA enhances monocytic cell adhesion to fibronectin by upregulating alpha(5)beta(1) integrin.
- Modulation of alpha(5)beta(1) expression is critical for regulating monocytic cell function during lung inflammation and injury.
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